Interdisciplinary approaches to extending the repertoire of ‘druggable’ targets. CLICK HERE FOR A HIGH RESOLUTION IMAGE. (a) A two dimensional representation of chemical space being partitioned for library construction and hit expansion into clusters of similar compounds using a simple sphere exclusion method (see Huggins et al, ACS Chemical Biology (2011). (b) Guiding the rational synthesis of chemical inhibitors against novel target classes. The panels show the X-ray crystal structures of a protein-protein interaction domain with and without a bound small-molecule inhibitor. (c) Probing biological function with small molecule inhibitors. The normal metaphase alignment of chromosomes (top row) is contrasted against the effects (bottom row) of an inhibitor of a mitotic protein-protein interaction.